Peritoneal dialysis is a method for exchanging solutes and water in capillary vessels of a patient's peritoneal membrane with a hypertonic solution, which is infused into the peritoneal cavity. The principle of this method is diffusion of solutes transferred according to the concentration gradient and water migration due to osmotic differences over the peritoneal membrane. This method has many advantages, e.g. that no special apparatus is commonly required, it gives less influence on the hemodynamics because extracorporeal circulation of the patient's blood is not necessary, and further the peritoneal dialysis is a continuous treatment and therefore more similar to the function of the kidneys.
Peritoneal dialysis is usually classified as continuous ambulatory peritoneal dialysis (CAPD), intermittent peritoneal dialysis (IPD), continuous cyclic peritoneal dialysis (CCPD) or automated peritoneal dialysis (APD).
In CAPD a catheter is permanently implanted in the abdominal wall of the patient and about 1.5 to 2.5 l of a dialysis fluid is normally introduced via the catheter into the peritoneal cavity. The peritoneal cavity is flooded with this fluid, left for an appropriate lapse of time and then drained. Removal of solutes and water takes place across the peritoneal membrane, which acts as a semi-permeable membrane.
The dialysis fluid normally used for peritoneal dialysis is an aqueous solution comprising an osmotic agent such as glucose and the like, electrolytes such as sodium, potassium, calcium, magnesium, and organic acid salts such as sodium lactate, sodium bicarbonate, and/or sodium pyruvate. The components of these peritoneal dialysis fluids are selected to control the levels of electrolytes or the acid-base equilibrium, to remove waste materials and to efficiently carry out ultrafiltration in order to keep the fluid balance correctly within the patient.
Inadequate fluid and solute transport is one very important reason for drop out from the peritoneal dialysis treatment. Continuous exposure of the peritoneal membrane to non-biocompatible solutions could cause an inflammation in the peritoneal membrane, and this might be one cause for the impaired function of the peritoneal membrane. This inflammatory reaction may involve complement and coagulation cascade and it has been demonstrated in clinical studies that complement and coagulation systems are activated in PD patients. The addition of heparin, which is known to inhibit complement and coagulation cascade, has been reported to decrease angiogenesis and also to increase ultrafiltration. An increased ultrafiltration will lead to an improved fluid and solute removal and patients can remain on PD for a longer period of time.
However, heparin and derivates thereof are difficult to use in PD fluids because the PD fluids are sterilised at high temperatures and heparin and the derivates thereof is not stable at such high temperatures. There are studies in which the patients are told to inject the substance, such as heparin, into the bag just before use, see e.g. EPO710483, but this is a complicated procedure for the patient.
In WO 01/21233 a dialysis fluid is disclosed comprising 0.8-6.67 mM citrate, preferably 0.8-5 mM and most preferably 1-3.33 mM citrate, 1.75-2.5 mM calcium ions, 0.5-1 mM magnesium ions and less than 60 g/L glucose. The advantages according to WO 01/21233 is that in a hemodialysis treatment a local anticoagulation is provided, which enhances blood flow through the artificial dialysis membrane, enhances the “dialysis dose”, keeps the artificial dialysis membrane cleaner, and give rise to a higher clearance of molecules with middle size (about 12 000 D).
In WO 00/23086 a dialysis fluid concentrate is disclosed, and one embodiment is a PD fluid, which, when ready for use, preferably comprises 0.17-2 mM citrate. Here the citrate is added to ensure proper pH within the dialysis fluid, and the preferred range to meet this in a PD solution is 0.17-2 mM citrate in the final PD fluid ready for use.
In U.S. Pat. No. 6,610,206 a dialysis fluid concentrate is disclosed, and one embodiment is a PD fluid, which, when ready for use, comprises 0.5-6 mEq/L citrate, which equals 0.17-2 mM citrate.
In EP 1 124 567 a dialysis fluid concentrate is disclosed, and one embodiment is a PD fluid, which, when ready for use, comprises 0.17-2 mM citrate.
In WO 98/29151 a dialysis fluid is disclosed, which is intended for use as a dialysis fluid for hemodialysis and which comprises 1-15 mM citrate. Also here, as in WO 01/21233, the citrate is added as a local anticoagulant within the artificial dialysis membrane.